1. Field of the Invention
The present invention relates to novel cephem compounds, their preparation and their use as antimicrobial agents, particularly, against Methicillin-Resistant Stapylococcus aureus (MRSA) and antimultipledrug-resistant bacteria.
2. Background Information
A variety of cephem compounds having both an aromatic or aliphatic quaternary ammonium methyl or propenyl group at the 3-position of a cephem skeleton and 2-(2-amino-thiazol-4-yl)- or 2-(5-amino-1,2,4-thiadiazol-3-yl)! -2-hydroxy (or substituted hydroxy) iminoacetamido group at the 7-position have so far been developed and many patent applications concerning those compounds, for instance, Japanese Patent Publication A (TOKKAISHO) Nos. 55-149289 (1980), 57-56485 (1982), 57-192394 (1982), 58-159498 (1983), 60-224694 (1985), 60-237090 (1985), 61-7280 (1986), 62-149682 (1987), 62-270589 (1987), and (TOKKAIHEI) Nos. 2-28170 (1990), 4-26692 (1992) and 7-41484 (1995) have been filed. However, the compounds of the present invention having substituted (or unsubstituted) 7-aminopyrazolo-1,5-a!pyrimidinium ring in a substituent at the 3-position of the cephem skeleton have not been disclosed.
Many Cephalosporin derivatives have been developed and cephem-type antibiotics have been widely used for the treatment of diseases of human beings and animals caused by pathogenic bacteria. However, the antimicrobial activities of those compounds are not sufficiently satisfactory. There is still a need therefore for compounds having excellent and broad antimicrobial activities against both gram-positive and gram-negative bacteria, for instance, against MRSA and against Pseudomonas aeruginosa.
As a result of extensive study on cephalosporin derivatives having a satisfactory antimicrobial activity against Gram-positive bacteria and also having strong antimicrobial activity against Gram negative bacteria, now it has been found that cephalosporin derivatives having 7-aminopyrazolo1,5-a!pyrimidine as substituents at the 3-position of the cephem skeleton have a wide antimicrobial spectrum against both Gram-positive bacteria and Gram-negative bacteria including MRSA and Pseudomonas aeruginosa.